As for questions about whether whey is meant to spur ketosis, I don't think so, but I admit I don't remember everything the doctor said when he recommended it. (The recommendation came before I'd read about *why* it might work, so I lacked a framework to integrate what he was saying. Much of the technical detail went, sadly, in one ear and out the other!)

One thing I do recall is he said to take it after my daily activities, (which is presumably a point where glycogen stores are diminished) where it might work as a PEM preventer.

It is whey protein isolate, hydrolysed, made with "cross-flow microfiltration." The brand is Dymatize ISO 100. I've bought whey only once, but I'd be surprised if there were not other types that are the same. As for dose, I'm taking one 31g scoop per diem, in water, but I will experiment over time.

(My sole objection to the whey is the size of the tub it comes in - it barely fits on the shelf. Perhaps that appeals to body builders on some subconscious level.)

The doc also recommended digestive enzymes, which I bought at the same time. They are still unopened - I'm trying to minimise the number of simultaneous changes for the sake of untangling cause and effect.

Yes trace the chain of causation using the knowledge that the offending agent is carried within the blood and can seemingly act on the cells of different people regardless of genetic differences, this seems to be a winning strategy, they said they can use filtration techniques either mechanical or otherwise to reduce it to certain types or groups.
Apparently there is a lot of different things in the blood though so it might take a while. Perhaps one form of that 'filtration' could be 'degradation', see how pervasive the agent is after being applied to live cells repeatedly, or vulnerable to heat / radiation damage, once you have that experiment that gives very interesting results theres lots of interesting things you can do with it.

Thanks for these thoughts Hip...Your hypothesis aligns with some of my results.

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I am not really offering a hypothesis as such. I am just saying I am not really clear on how processing the lactic acid from exercise via liver Cori cycle could worsen PEM, or have much affect on ME/CFS, which what they propose in the Myhill, Booth and McLaren-Howard Papers.

Though possibly the acidosis due to lactic acid might play a role in ME/CFS. In the MBM 2012 paper they mention something along these lines:

Glycolysis without the ETC results in lactate production, acidosis, and cellular damage. Athletes usually recover quickly because via training they have adjusted the proportions of type I and type II muscle fibers according to their discipline, and they normally use increased glycolysis for only short time intervals.

If patients with ME/CFS have to use increased glycolysis on a regular basis they will suffer from its results. The conversion of lactate back to pyruvate (via the Cori cycle) requires 6 molecules of ATP which must be made available and for patients this extends the time-scale of the lactic acid burn.

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ETC = electron transport chain (found within the mitochondria).

So what they may be saying in this paper (if I understood it correctly) is that because it takes a lot of energy to convert lactate back to pyruvate in the Cori cycle in the liver, and because ME/CFS patients are short of energy, the lactic acid created from exercise will be hanging around for a longer time than usual in the body, because the Cori cycle may be running slow due to poor energy supplies.

So ME/CFS patients may not only be creating more lactic acid from exercise (because their defect mitochondria may force them to use anaerobic glycolysis); but in addition, it may take them longer to clear this lactic acid, due to a slow Cori cycle.

Which means the lactic acid will be hanging around f or a long time, causing acidosis and cellular damage, according to the MBM 2012 paper.

Something is missing here. Not sure this covers all the bases. What about PEM triggered by concentration?

Exchange exertion for exercise - it will not be the same, and I think it needs to be.

Same holds true for strident emotions, except this more readily and overtly involves muscle extremes. But intellectual exertion PEM? How does that fit? Or the simple act of focusing too long or too hard?

The puzzle is trickier than some people seem to be implying and stating that we should just try a ketogenic diet and hope everything will be okay is simplistic.

....

The puzzle is more complicated than at first glance and there seem to be a few missing pieces...

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Agreed. I'd also read stuff about issues with the KREB cycle and we know some of us have issues with Methylation (which by itself has been ruled out from being an issue for everyone.

I'm betting that any one person can survive and handle ONE of the cycles not working at par. Add stressor or toxin or virus load and introduce damage to another metabolism pathway or to more than one and I'm betting it's a combination factor that leads to a point where people start seeing serious issues.

While I'm with everyone's eagerness to try to find something ANYTHING that can help us... I think we're just looking at the tip of the ice burg and we still have a lot to learn. The exciting bit is that I'm thinking we've finally found an ice burg instead of a bunch of false leads. This feels like it can lead somewhere real.

Something is missing here. Not sure this covers all the bases. What about PEM triggered by concentration?

Exchange exertion for exercise - it will not be the same, and I think it needs to be.

Same holds true for strident emotions, except this more readily and overtly involves muscle extremes. But intellectual exertion PEM? How does that fit? Or the simple act of focusing too long or too hard?

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Intellectual work requires more glucose to the brain. It's a work out for the brain.

But intellectual exertion PEM? How does that fit? Or the simple act of focusing too long or too hard?

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Post-exertional malaise from mental exertion could be explained by the same hypothesized mechanism for PEM that Myhill, Booth and McLaren-Howard (MBM) propose — a mechanism which is described in this post.

In brief, the mechanism MBM propose is that a temporary loss of ATP molecules, which results from putting a defective cellular energy metabolism under strain, is the cause of PEM. You only get over PEM once these lost ATP molecules are remanufactured from scratch (via de novo synthesis, which can take several days — hence why PEM can last several days).

Quite possibly this loss of ATP molecules could also occur in brain cells when there is significant mental exertion, thereby causing worsened cognitive and neuropsychological symptoms afterwards.

It's early days for this line of research but it would have been preferable if they had used additional control groups - e.g. sedentary controls or controls with metabolic syndrome (where reduced PDH complex activity/increased PDK expression is also found).

Our findings suggest that abnormal lactate responses to exercise in some patients with chronic fatigue syndrome are unlikely to be due solely to inactivity. Although we found no abnormalities of mitochondrial structure, the relative deficiency of type 1 muscle fibres is in keeping with other reports concerning reduced oxidative metabolism and mitochondrial enzyme activity in muscle in some patients with chronic fatigue syndrome.5-750Whether this deficiency is due to changes in muscle activity patterns or more fundamental disorders of mitochondrial function remains to be determined.

@Sasha Early on in this disease I had benefits from amino acid powder, but the effect diminished over a month or two, so it was another thing I crossed off the list. Right now I get 80g of hydrolyzed whey protein per day in enteral feeding formula which is the next closest thing to free amino acids and get no energy improvements from it either.

It is whey protein isolate, hydrolysed, made with "cross-flow microfiltration." The brand is Dymatize ISO 100. I've bought whey only once, but I'd be surprised if there were not other types that are the same. As for dose, I'm taking one 31g scoop per diem, in water, but I will experiment over time.

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Thanks, Murph - that's very helpful. I see that particular brand always comes flavoured (vanilla, chocolate, banana, etc.) which might cause migraines for me so I'll have to see if there's a nonflavoured brand with a similar amino acid profile. (I'm a bit worried that any of the amino acid products are going to give me migraines any, because tyramine seems to trigger migraines for me, as well as strong flavours, but all I can do is give it a go!)

I'd really like to thank those who brought up primary biliary cirrhosis as a possibility. My symptoms match pretty well (especially my itchy skin!) I spent the evening reading about it and am going to test the theory that it's an extension of celiac disease/gluten enteropathy.

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I just saw a gastroenterologist for the specific purpose of ruling out Primary Biliary Cirrhosis as it is one of few diseases other than ME/CFS that are known to cause post exertional malaise, plus I have a lot of itching, I have an enlarged spleen, and have been more jaundiced than usual (i have a hereditary blood disease that causes me to always be jaundiced). Plus my mother died of liver failure in her early 50's and I do not know details of why. So I wanted to be certain to rule PBC out.

The blood tests came back last week and thankfully I do not have PBC.

If you really are worried you may have PBC you should be evaluated immediately as the sooner treatment is begun the less likely a liver transplant will be needed in the future and better chance of a normal life span. Sadly a large % of those with PBC have no symptoms until the disease has already caused significant damage to the liver.

I learned very quickly that physical exertion made me very sick... By chance I began eating what I would describe as a very healthy diet after I got out of hospital (low sugar, quite low carbs, lots of veggies, healthy meats)...around the same time I got an incredible appetite-- I still have recordings where I literally started to need to eat twice as much as usual-- because I couldn't keep up with demands I added a meal replacements high in protein and amino acids etc twice a day as well as heaps of other 'healthy' food...Within another 3 weeks I started feeling much better rally quickly (went from being apartment bound to walking 500 metres in a week)...

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I've been increasing my aa and protein intake for some days now and I have felt that urge to increase meals too. The hunger is unbearable. At first I thought there might be some bacterial/candida infection going on, but maybe I'm experiencing what you did.

using the knowledge that the offending agent is carried within the blood and can seemingly act on the cells of different people regardless of genetic differences, this seems to be a winning strategy, they said they can use filtration techniques either mechanical or otherwise to reduce it to certain types or groups.

Whey protein improved my symptoms dramatically, but I dropped it when I dropped milk products. I'm encouraged to hear that casein is what bothers a lot of people, but I'm not certain that's the case for me.

I've been increasing my aa and protein intake for some days now and I have felt that urge to increase meals too. The hunger is unbearable. At first I thought there might be some bacterial/candida infection going on, but maybe I'm experiencing what you did.

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Same thing happens to me. Think its pretty standard when carbs are cut out. Veggies just dont keep you full for long and the body seems to process them much quicker